Blood, 1 June 2002, Vol. 99, No. 11, pp. 3883-3884
CD4 T cells to kiss off chemotherapy-resistant CMV?
Riddell and coworkers (Science. 1992;257:238-241) have shown
that infusions of donor CD8 T cells with specificity for
cytomegalovirus (CMV) can prevent viremia and clinical complications in
patients undergoing allogeneic stem cell
transplantation. In this issue, Einsele and colleagues
(page 3916) report results following the infusion of donor T-cell lines
for therapeutic intervention in the setting of
chemotherapy-resistant CMV infection. A single infusion of T cells
resulted in the clearing of CMV viremia in 5 of 7 patients, and a
second infusion was associated with resolution of viremia in an
additional patient, so that 6 of 7 patients had resolution of CMV.
These studies extend previous studies because they suggest T-cell
infusions comprising predominantly the CD4 subset may be
efficient for the control of CMV viremia in immunosuppressed patients.
It is also clear that CD8 cytotoxic T cells are required for the
control of CMV infection, and this study, along with others, illustrates the critical requirement for CD4 cells in the control of
many chronic viral infections.
Adoptive transfer of T cells for control of infections with CMV and
Epstein-Barr virus has documented efficacy in the setting of
immunosuppression, and studies show promise for patients with HIV
infection. But there are several issues to be resolved before this
procedure becomes a routine therapy for patients with severe viral
infections. First, more efficient culture systems will aid in the
delivery of this therapy. In this study, 4 repetitive stimulations with
antigen-presenting cells were carried out in vitro before
sufficient cells were available for therapy. Second, recent studies
indicate that naive T cells emigrating from the thymus undergo
differentiation to activated T cells, central memory T cells,
peripheral effector T cells, and peripheral memory T cells. It is
likely that optimal infusions would consist predominantly of
central memory T cells in the prophylactic setting, while in the
therapeutic setting T-cell infusions should be biased toward peripheral
effector cells and peripheral memory T cells. Advances in present
culture techniques will be required in order to address this issue.
Finally, it is sobering to note that, despite control of CMV viremia in
6 of 7 patients, 3 patients subsequently developed invasive
aspergillosis or respiratory syncytial virus interstitial pneumonitis
in this study. Therefore, a comprehensive approach to reconstitute
immunity in immunosuppressed patients is required.
Carl H. June
University of Pennsylvania
